Invasion of the Nervous System. Author Orkide Koyuncu, Lynn Enquist, Esteban Engel Publication Year 2021 Type Journal Article Abstract In vertebrates, the nervous system (NS) is composed of a peripheral collection of neurons (the peripheral nervous system, PNS), a central set found in the brain and spinal cord (the central nervous system, CNS). The NS is protected by rather complicated multi-layer barriers that allow access to nutrients and facilitate contact with the peripheral tissues, but block entry of pathogens and toxins. Virus infections usually begin in peripheral tissues and if these barriers are weakened, they can spread into the PNS and more rarely into the CNS. Most viral infections of the NS are opportunistic or accidental pathogens that gain access via the bloodstream (e.g., HIV and various arboviruses). But a few have evolved to enter the NS efficiently by invading neurons directly and by exploiting neuronal cell biology (e.g., rhabdoviruses and alphaherpesviruses). Most NS infections are devastating and difficult to manage. Remarkably, the alphaherpesviruses establish life-long quiescent infections in the PNS, with rare but often serious CNS pathology. In this review, we will focus on how alphaherpesviruses gain access to and spread in the NS, with particular emphasis on bidirectional transport and spread within and between neurons and neural circuits, which is regulated by complex viral-host protein interactions. Finally, we will describe the wide use of alphaherpesviruses as tools to study nerve connectivity and function in animal models. Keywords Animals, Humans, Neurons, Central Nervous System, Alphaherpesvirinae, Peripheral Nervous System, Herpesviridae Infections Journal Curr Issues Mol Biol Volume 41 Pages 1-62 Date Published 2021 ISSN Number 1467-3045 DOI 10.21775/cimb.041.001 Alternate Journal Curr Issues Mol Biol PMID 32723924 PubMedGoogle ScholarBibTeXEndNote X3 XML